Evaluation of distortion and transient evoked otoacoustic emission in tinnitus patients with normal hearing.

INTRODUCTION
Tinnitus is a perception of sound without external source. The exact etiology of tinnitus is not fully understood, although some researchers believe that the condition usually starts in the cochlea. The aim of this study was to determine the potential contribution of outer hair cell dysfunction to chronic tinnitus, by application of Distortion-Product Evoked Otoacoustic Emission (DPOAE) and Transient Evoked Otoacoustic Emission (TEOAE) and also to determine the relationship between tinnitus loudness and the amplitude of these two potentials.


MATERIALS AND METHODS
This study was conducted on 20 tinnitus patients aged 20-45 years and 20 age- and gender-matched control subjects. DPOAE and TEOAE were performed on each subject.


RESULTS
The difference in the amplitudes of TEOAE between the two groups was not significantly different (P=0.08), but the amplitude of DPOAE in patients with tinnitus was significantly lower than the corresponding value in the control subjects (P=0.01). There was no correlation between tinnitus loudness and the amplitudes of neither DPOAE nor TEOAE.


CONCLUSION
Abnormal findings in the DPOAE of tinnitus sufferers suggest some form of cochlear dysfunction in these patients. As there was no correlation between the amplitude of the recorded potentials and tinnitus loudness, factors other than cochlear dysfunction may also influence the loudness of tinnitus.


Introduction
Tinnitus, from the Latin word tinnire, meaning "to ring," is a phantom perception of sound when no such sound is present externally (1). Tinnitus affects the quality of life of millions of people around the world and is associated in most cases with hearing impairment (2). Although most incidences of tinnitus are temporary, chronic subjective tinnitus occurs in 4-15% of the general population, with the prevalence increasing in those above 50 years of age to almost 20% (3). Broadly speaking, approximately 90% of individuals with chronic tinnitus have some form of hearing loss; however, only about 30-40% of those with hearing loss develop tinnitus (4,5). For instance, Barnea et al. (1990) found that 8% of patients with tinnitus had normal hearing thresholds up to 8,000 Hz (defined as better than or equal to 20 dBHL) (6). As reported by the National Center for Health Statistics, tinnitus affects approximately 12% of people between the ages of 65-74 years, and the prevalence of hearing impairment in the tinnitus population is between 80 and 90% (1).
Many theories have been presented in an attempt to explain the origin of tinnitus in patients with normal hearing. Although tinnitus may be associated with abnormalities at any level of the auditory pathway, it very often starts in the cochlea. Indeed, Jastreboff et al (1993) considers that tinnitus usually starts in the cochlea and generates abnormal activity in the central pathways, which prolongs the systems; the central auditory pathways do not need to be structurally altered (7). It was hypothesized that small cochlear abnormalities can result in tinnitus, even before any hearing loss is apparent (8,9).
Otoacoustic emissions (OAEs) are a propagation of the audiofrequency signal into the ear canal from the cochlea, transmitted through the ossicular chain and tympanum. They are believed to originate from an active mechanical force generated by the outer hair cells (8).
OAEs are an important tool for the objective evaluation of the inner ear function, especially the outer hair cells of the cochlea. They occur in response to acoustical stimulation, or can even appear spontaneously. Otoacoustic emissions can be evoked by a broadband stimulus (a click) or by brief tones (9).
As otoacoustic emissions are invariably associated with functioning outer hair cells (OHC), their presence is a reliable indicator of cochlear structural integrity, and their absence may indicate a cochlear lesion. Furthermore, by recording otoacoustic emissions, a subclinical cochlear lesion may be detected, as up to 30% of the OHC population may experience damage before any audiometric evidence is apparent in the quarter octaves pure-tone audiometry from 0.125 kHz to 16 kHz. Therefore, we selected this test to evaluate the cochlea in tinnitus patients (10).
The aim of this study was to evaluate cochlear function in tinnitus patients; in other words, we wanted to determine whether or not tinnitus occurs because of a dysfunction at the level of the OHCs. In this study, we used evoked otoacoustic emissions (EOAE) to assess the function of the OHCs in tinnitus patients with normal hearing.

Materials and Methods
Subjects: The patient group consisted of 20 adult males with subjective tinnitus (bilateral or unilateral) who had normal hearing thresholds as revealed by pure-tone and speech audiometry measurements who attended an audiology clinic in a university center, from June 2011-July 2012. Normal hearing was defined as a hearing level of 20 dB or less at all audiometric frequencies (250, 500, 1,000, 2,000, 4,000, 6,000, 8000, 12,000, and 16,000 Hz). A group of 20 healthy male subjects with normal hearing and no history of tinnitus or auditory or vestibular symptoms participated as a control group. The two populations had similar gender and age distribution. All patients had a definitive diagnosis of subjective tinnitus that lasted more than 1 month, as well as a thorough medical history and clinical examination verified by an otologist. The following exclusion criteria for both the patient and control groups were applied at baseline: history of familial hearing loss, tinnitus perception less than 1 month, use of ototoxic drugs, chronic otitis media, head trauma, and age >45 years.
Subjects were seated in an acoustically test chamber. First, pure-tone audiometry, tympanometry, and stapedial muscle reflex were performed, and then the pitch and loudness of tinnitus was evaluated. In this measurement we asked the patient to compare the pitch produced by a noise or pure tone to the most prominent pitch of tinnitus. They then adjusted the intensity of a noise or tone so that it had the same loudness as their tinnitus.
Next we evaluated otoacoustic emission. The first ear examined was the right ear in patients with bilateral tinnitus; while in unilateral patients we first assessed the affected ear. TEOAE testing always was performed first. TEOAEs were performed with a wide band click in a continuous mode and an intensity of 80 dB peak sound pressure level (SPL). For measuring distortion product (DP) grams, the frequency separation of the primaries was f2/f1 = 1.22, with L1 and L2 set to 65 and 55 dB SPL, respectively.
The following parameters were considered in the TEOAE tests: 1) signal-to-noise (S/N) ratio_6 dB 2) and reproducibility of the responses of at least 70%. In the DPOAE, the parameters of interest in all tested frequencies were: 1) S/N ratio_6 dB in; 2) amplitude of the signal in the 90 th percentile of the normal distribution for the frequencies tested; 3) only the frequencies from 1,000 to 8,000 Hz were considered.

Statistical Analysis
All data were analyzed using SPSS version 16.0 (Chicago, IL, USA), including routine statistical procedures such as Leven's independent t test, Mann-Whitney U test, and one-way analysis of variance (ANOVA), at the significance level of P<0.05.

Results
Mean (± standard deviation) of age was 29/10 (± 6/43) years for patients and 28/40 (±6/02) years for controls. There was no statistically significant difference between the two groups with respect to gender or age (P>0.05).

Pure-Tone Audiometry
Results of pure-tone audiometry confirmed normal hearing in all subjects, and there were no significant differences in the mean threshold levels between the groups (P>0.05). The results of audiometric test are shown in (Table. 1).

Tympanometry
Tympanometric measures in all subjects were within normal ranges and the middle ear pressure was comparable between the groups.

Acoustic Reflexes
In all subjects, acoustic reflexes, ipsilateral and contralateral, were lower than 110 dB across at least three adjacent frequencies.

Otoacoustic Emission Tests
We chose TEOAE and DPOAE because they are the most commonly used OAE tests in clinical practice and also they have more standardized methodology. The criteria for normality are stated in the Materials and Methods section.

TEOAEs
There was no significant difference between the mean of overall TEOAE amplitude in patients with bilateral tinnitus, unilateral tinnitus, and normal subjects (P>0.05) ( Table.2).

DPOAEs
The mean of overall DPOAE amplitudes in patients with tinnitus was significantly lower than the corresponding value in normal subjects (P<0.05); however, there was no difference between patients with unilateral and bilateral tinnitus (Table. 3). Our comparison between the amplitude of DPOAE in tinnitus patients and normal subjects was in the frequency of tinnitus, which we defined through the pitchmatching test for each patient.

Correlation Between Tinnitus Loudness and DPOAE Results
Pearson's correlation coefficient was used to evaluate the degree of agreement between tinnitus loudness and DPOAE in the tinnitus patients. There was no correlation between tinnitus loudness and the amplitude of DPOAE in patients with tinnitus (P>0.05).

Discussion
Tinnitus is an otologic symptom and, despite considerable research in this field, the exact pathophysiological processes of tinnitus remain unknown. Involvement of the whole auditory system, either peripheral or central, should be considered in the generation of tinnitus.
Some hypothesized pathomechanisms and causes of tinnitus include spontaneous otoacoustic emissions, edge theory, discordant theory, dorsal cochlear nucleus, hyperactivity/plastic readjustment of dorsal cochlear nuclei (DCN), crosstalk theory, pharmacological causes, and neurologic disorders (11).As the cause and the perception of tinnitus are so heterogeneous, an etiologic subdivision of tinnitus population is essential to achieve an effective treatment (12).
The high incidence rate of cochlear damage and studies of cochlear mechanics have led to the suggestion that tinnitus at themed and high frequencies might, in many cases, arise from the cochlea; although the possibility that an acute exacerbation of tinnitus may result from changes in the efferent nervous system has also been suggested (13). A cochlear disorder, even when undiagnosed by puretone audiometry, may initiate a series of processes in the nervous system that may result in tinnitus (15).  Hesse et al (2005), of DPOAE in tinnitus sufferers which showed that reduced OHC activity, as detected by reduced DPOAE levels, may manifest as tinnitus even before there is a shift in hearing threshold (19,20). We assumed that the difference between the results of TEOAE and DPOAE is because the DPOAEs are considered to have a higher sensitivity. Therefore, we recorded DPOAE with a lower amplitude in comparison with TEOAE. We found no relationship between tinnitus loudness and the magnitude of OHC damage, meaning that factors other than cochlear dysfunction may affect tinnitus loudness.

Conclusion
Patients with normal hearing who have tinnitus may have cochlear damage. Although referring to a limited population, this observation might be useful in the attempt to elucidate the mechanisms of tinnitus generation and perception. We concluded that DPOAE is a more useful tool in an estimating cochlear damage in tinnitus patients with normal hearing. Further studies with a larger sample size and using other audiometric tests are needed for further evaluation of the mechanism of tinnitus generation.